Self-Assembled Ferritin Nanoparticles Expressing Hemagglutinin as an Influenza Vaccine

NIH inventors at the Vaccine Research Center have developed a novel influenza virus hemagglutinin (HA)-ferritin nanoparticle influenza vaccine that is easily manufactured, potent, and elicits broadly neutralizing influenza antibodies against multiple strains of influenza. This novel influenza nanoparticle vaccine elicited two types of broadly neutralizing, cross-protective antibodies, one directed to the highly conserved HA stem and a second proximal to the conserved receptor binding site (RBS) of the viral HA, providing a new platform for universal and seasonal influenza.

Stabilized Influenza Hemagglutinin Stem Region Trimers and Uses Thereof

An effective universal influenza vaccine would eliminate the uncertain and costly process of seasonal influenza vaccine development each year. Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) are developing immunogens which elicit neutralizing antibodies to the highly conserved stem region of the influenza viral protein hemagglutinin.

Neutralizing Antibodies to Influenza HA and Their Use and Identification

The effectiveness of current influenza vaccines varies by strain and season, in part because influenza viruses continuously evolve to evade human immune responses. While the majority of seasonal influenza infections cause relatively mild symptoms, each year influenza virus infections result in over 500,000 hospitalizations in the United States and Europe. Current standard of care for individuals hospitalized with uncomplicated influenza infection is administration of neuraminidase inhibitors.

Stabilized Group 2 Influenza Hemagglutinin Stem Region Trimers and Uses Thereof

Researchers at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID) have designed influenza vaccine candidates based on group 2 influenza hemagglutinin (HA) proteins. These group 2 HA proteins were engineered to remove the highly variable head region and stabilize the remaining stem region. The researchers then fused the engineered group 2 HA stabilized stem with a ferritin subunit. The resulting fusion protein can self-assemble into nanoparticles which display group 2 HA stem domain trimers on their surface.

Novel Multivalent Nanoparticle Vaccines

Current seasonal influenza vaccines are designed to elicit immunity to circulating strains of influenza each year. The targeted strains are selected based on predictions of which strains are likely to be predominant in the human population for a given year. This prediction must be made well ahead of the influenza season to allow time for vaccine production and can be inaccurate.

Chimeric SHIV Gag Proteins Optimize T-Cell Response Against HIV Gag

HIV Gag has been included in nearly all HIV vaccines entering clinical trials because of its importance in SIV models and its correlation with protection in HIV-infected long-term non-progressors. However, HIV Gag has proven less immunogenic than Env in phase I clinical trial studies. Through sequence comparison, two regions in HIV Gag have been identified as contributing to the decreased immunogenicity observed for HIV Gag. Replacement of these regions with corresponding SIV sequences significantly increased the resulting T-cell response to HIV Gag in mice.

Increased Protein Expression Vector for Vaccine Applications

An expression vector with a unique promoter that results in higher level of protein expression than vectors currently in use is available for licensing from the NIH. The elevated levels of expression are achieved through use of a specific promoter, known as CMV/R, in which the Human T-Lymphotrophic Virus (HTLV-1) Long Terminal Repeat (LTR) R-U5 region is substituted for a portion of the intron downstream of the CMV immediate early region 1 enhancer (Barouch et al., 2005). Sequences of 95% or better homology to CMV/R can be used as well.

Programmable and Modular Nucleic Acid Nanoassemblies-based (NAN) Platforms to Regulate Mechanosensitive Activation of T-cells

This technology includes mechanobiological nucleic acid nanoassemblies-based platforms with dynamically controlled efficiency of T-cell activation. T-cells are the central players in adaptive immune response led by a T-cell receptor (TCR) centric machinery. Current T-cell activation strategy (e.g., micron-scale beads) focuses on 2D TCR-agonist biomimetic surfaces and biomimetic 2D immune synapses with planar traction, which requires non-physiological hyper-stimulatory cytokines levels (e.g., IL-2), and thus, is incompatible with clinical applications.

Micro-Dose Calibrator for Pre-clinical Radiotracer Assays

Molecular imaging is a disease-specific targeting modality that promises much more accurate diagnoses of serious diseases such as cancer and infections. Agents are being continually developed with a view to clinical translation, with several such therapies requiring measurement of very small doses. Currently, there is no way of accurately measuring small amounts of radioactivity used in many pre-clinical tracer studies, as on-the-market commercial dose calibrators measure at too high a dose range, typically at 10-1000 µCi and higher.

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